The healing of wounds is a complex process which is often further complicated by the presence of non-viable, necrotic tissue in the wound area. Debridement is the process of removing the non-viable tissue from a wound to prevent infection and facilitate healing.
Considerable efforts have been made to discover materials capable of distinguishing between viable and non-viable tissue. The discovery of materials which would digest devitalized tissue while not attacking viable tissue would make it possible to remove the devitalized tissue without surgery. It would be a beneficial therapeutic agent in virtually all disease processes or injuries where topically devitalized tissue needs to be removed from the wound area such as burns, cutaneous ulcers, pressure necroses, incisional, traumatic and pyogenic wounds, and ulcers secondary to peripheral vascular disease.
One area that has attracted considerable attention is the use of proteolytic enzymes and other chemicals to effect the early debridement of necrotic tissue from cutaneous ulcers and from burns. Such devitalized tissue is an excellent culture medium for microorganisms and moreover is the principal source of the septicemia which is the proximate cause of death, for example, in the majority of severely burned patients.
Devitalized tissue, which is commonly referred to as eschar, from cutaneous ulcers or burns is a complex mixture of dried blood, purulent exudates, and denatured proteins normally found in the epidermal and dermal skin layers. The denatured proteins found in eschar are primarily collagen, elastin, fibrin, hemoglobin, and other coagulated proteins.
Collagen comprises about 75% of the skin's dry weight and is the main constituent of the necrotic debris and of eschar. Strands of semi-viable, compromised collagen, whose protective mucopolysaccharide sheath has been damaged or destroyed, anchor the necrotic tissue to the wound surface. These strands must be fully eliminated in order for the necrotic material to be separated from its base. This complete debridement then permits development of granulation tissue during the healing process.
For a proteolytic enzyme to be suitable for use as a debriding agent, it is desirable for the protease to distinguish between viable and non-viable tissue; readily and thoroughly hydrolyze the wide variety of denatured proteins found in eschar; function at physiological pH and temperature; be compatible with adjunct therapies (e.g., cleansing agents, topical antibiotics); not interfere with normal wound healing; and remain stable in various formulations and at a wide range of temperatures. Furthermore, treatment of burn wounds with proteases should not complicate skin grafting. A number of proteolytic enzyme preparations have been used as debriding agents with varying degrees of success.
However, one problem associated therewith is that obtaining stable formulations of proteolytic enzymes is often problematic. A hydrophobic formulation is a water-in-oil emulsion, whereas a hydrophilic formulation is an oil-in-water emulsion. Most proteolytic enzymes are formulated into hydrophobic formulations and must be stored at refrigerated temperatures to stabilize the enzymes. For this reason, there are definite disadvantages of hydrophobic formulations. The disadvantages include the necessity to raise temperatures of the preparation before administration, reduced accessibility of the enzyme to the administration site, and difficulty in removing the formulation from the administration site by gentle cleansing procedures.
The composition of the invention overcomes the difficulties of the prior art by providing a hydrophilic formulation which stabilizes an enzyme, preferably a protease and more preferably a Vibrio protease and maintains the stability at ambient temperatures. Therefore, it is well suited for use as a therapeutic agent.